Tacrolimus (FK506) suppresses TREM-1 expression at an early but not at a late stage in a murine model of fungal keratitis.
Tacrolimus (FK506) suppresses TREM-1 expression at an early but not at a late stage in a murine model of fungal keratitis.
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他克莫司 (FK506) 在真菌性角膜炎小鼠模型的早期阶段抑制 TREM-1 表达，但在晚期阶段则不然。
DOI：
10.1371/journal.pone.0114386
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Huang W;Ling S;Jia X;Lin B;Huang X;Zhong J;Li W;Lin X;Sun Y;Yuan J
目的探讨新型大环内酯类免疫抑制剂他克莫司（FK 506）对烟曲霉诱导的小鼠角膜炎模型髓样细胞触发受体-1（TREM-1）表达的抑制作用及其机制。 通过实时定量PCR（qRT-PCR）检测11个真菌感染的人角膜中的TREM-1。将RAW264.7巨噬细胞分为4组，分别接受酵母聚糖（100 µg/ml）、酵母聚糖（100 µg/ml）+ mTREM-1/Fc蛋白（1 µg/ml）或酵母聚糖（100 µg/ml）+FK 506（20 µM）处理或阴性对照处理。采用qRT-PCR和ELISA法检测TREM-1、白细胞介素-1 β（IL-1β）和肿瘤坏死因子α（TNFα）的表达。采用烟曲霉菌角膜基质内注射法建立小鼠真菌性角膜炎模型，分为2组：A组给予溶媒滴眼液，每日4次; B组给予FK 506滴眼液，每日4次。通过临床评分和组织学检查评估角膜损伤，并采用ELISA法检测髓过氧化物酶（MPO）蛋白水平。然后使用qRT-PCR和ELISA在不同时间点测定TREM-1、IL-1β和TNFα的表达。在患有真菌性角膜炎的人角膜中，TREM-1表达显著增加。相反，FK 506可降低酵母多糖刺激的RAW 264.7巨噬细胞中TREM-1、IL-1β和TNFα的表达。在小鼠模型中，在感染后第1天，FK 506治疗组的角膜评分低于对照组，多形核中性粒细胞（PMN）浸润减少。TREM-1、IL-1β和TNFα表达在同一时间点显著降低。然而，在感染后5天，细胞因子表达、临床评分和浸润的统计学显著差异消失。FK 506可能通过下调TREM-1的表达，抑制真菌性角膜炎的炎症反应，减轻真菌性角膜炎早期角膜损伤的严重程度。
To investigate the efficacy and mechanism of tacrolimus(FK506), which is a novel macrolide immunosuppressant, in inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) expression in a murine keratitis model induced by Aspergillus fumigatus. TREM-1 was detected in 11 fungus-infected human corneas by quantitative real-time PCR (qRT-PCR). RAW264.7 macrophages were divided into four groups, which received treatment with zymosan (100 µg/ml), zymosan (100 µg/ml) + mTREM-1/Fc protein (1 µg/ml), or zymosan (100 µg/ml) + FK506 (20 µM) or negative-control treatment. After this treatment, the expression of TREM-1, interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) was assayed using qRT-PCR and ELISA. The mouse model of fungal keratitis was created by intrastromal injection with Aspergillus fumigatus, and the mice were divided into 2 groups: group A received vehicle eye drops 4 times each day, and group B received 4 doses of FK506 eye drops each day. Corneal damage was evaluated by clinical scoring and histologic examination,and myeloperoxidase (MPO) protein levels were also detected by ELISA. The expression of TREM-1, IL-1β and TNFα was then determined at different time points using qRT-PCR and ELISA. TREM-1 expression dramatically increased in the human corneas with fungal keratitis. In contrast, FK506 reduced the expression of TREM-1, IL-1β and TNFα in RAW264.7 macrophages stimulated with zymosan. In the mouse model, at day 1 post-infection, the corneal score of the FK506-treated group was lower than that of the control, and polymorphonuclear neutrophil (PMN) infiltration was diminished. TREM-1, IL-1β and TNFα expression was significantly reduced at the same time point. However, the statistically significant differences in cytokine expression, clinical scores and infiltration disappeared at 5 days post-infection. FK506 may inhibit the inflammation induced by fungi and alleviate the severity of corneal damage at an early stage of fungal keratitis by downregulating TREM-1 expression.
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影响因子：
4.3
作者：
KEICHO, N;SAWADA, S;TAKAKU, F
通讯作者：
TAKAKU, F
DOI：
10.1111/j.1749-6632.2012.06837.x
发表时间：
2012-01-01
期刊：
ADVANCES AGAINST ASPERGILLOSIS II
影响因子：
--
作者：
Mansour, Michael K.;Tam, Jenny M.;Vyas, Jatin M.
通讯作者：
Vyas, Jatin M.
Dectin-1介导β-葡聚糖的生物学作用。
DOI：
10.1084/jem.20021890
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown GD;Herre J;Williams DL;Willment JA;Marshall AS;Gordon S
通讯作者：
Gordon S
影响因子：
15.3
作者：
Gibot, S;Kolopp-Sarda, MN;Béné, MC;Bollaert, PE;Lozniewski, A;Mory, F;Levy, B;Faure, GC
通讯作者：
Faure, GC
影响因子：
8.3
作者：
LIU, T;CLARK, RK;FEUERSTEIN, GZ
通讯作者：
FEUERSTEIN, GZ